Organocatalytic enantioselective synthesis of tetrasubstituted chiral allenes via 1,12-addition of alkynyl aza-biphenyl quinone methides formed in situ

Abstract

The development of organocatalytic remote stereocontrolled conjugate additions, though highly desirable, remains a formidable challenge in asymmetric synthesis. Herein, we report a chiral phosphoric acid-catalyzed 1,12-conjugate addition of in situ-generated aza-4,4′-biphenyl quinone methides (aza-4,4′-BQMs), derived from α-functionalized alcohols, with indole-2-carboxylates. This reaction provides efficient access to axially chiral tetrasubstituted allenes in high yields with good to excellent enantioselectivities. Notably, this work not only extends the applicability of alkynyl 4,4′-BQMs to their aza-analogues but also accomplishes the first enantioselective 1,12-addition of alkynyl aza-4,4′-BQMs, representing a significant advancement in quinone methide chemistry.